National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
Mol Diagn Ther. 2020 Dec;24(6):703-713. doi: 10.1007/s40291-020-00493-4. Epub 2020 Sep 25.
Early diagnosis and biomarker-based ante-mortem tests are essential in efforts against the development of neurodegenerative diseases and can be considered primary neuroprotective measures. Blood is the ideal biofluid for a routine ante-mortem screening test. However, biomarker discovery in the blood is particularly difficult because of interference from factors both intrinsic and extrinsic to blood with the detection of hallmark neurodegenerative biomarkers, such as the pathological prion protein, amyloid-β, and others. Blood extracellular vesicles (EVs), such as exosomes, are cell-derived vesicles released into the blood from all parts of the body (including the brain and spinal cord). They are an enriched source of neural-derived EVs containing neurodegenerative biomarkers that mirror (in the blood) the condition present in the brain. The feasibility of using, and the reliability of, neural-derived blood EVs (NDBEVs) as a method of diagnosing Alzheimer disease and other neurodegenerative diseases has been assessed in strong proof-of-concept studies. Results from these studies strongly suggest that NDBEVs might represent the right strategy for specific, reliable, and early diagnosis of neurodegenerative diseases. Based on these results, NDBEVs might enable the creation of an ante-mortem blood test (liquid biopsy of the brain) for neurodegenerative diseases. This would enormously accelerate the therapy of neurodegenerative diseases. This review highlights the powerful potential of liquid biopsy of the brain using NDBEVs for early diagnosis and treatment of neurodegenerative diseases, and the challenges and limitations related to the identification of clinically applicable EV (exosomal) biomarkers using blood are discussed.
早期诊断和基于生物标志物的生前测试对于对抗神经退行性疾病的发展至关重要，可以被视为主要的神经保护措施。血液是进行常规生前筛选测试的理想生物流体。然而，由于血液中存在内在和外在的干扰因素，使得生物标志物的发现特别困难，这些因素会干扰标志性神经退行性生物标志物的检测，如病理性朊病毒、淀粉样β蛋白等。血液细胞外囊泡（EVs），如外泌体，是从身体各个部位（包括大脑和脊髓）释放到血液中的细胞衍生囊泡。它们是富含神经源性 EVs 的来源，其中包含与大脑中存在的情况相镜像的神经退行性生物标志物。使用神经源性血液 EVs（NDBEVs）作为诊断阿尔茨海默病和其他神经退行性疾病的方法的可行性，以及其可靠性，已经在强有力的概念验证研究中得到了评估。这些研究的结果强烈表明，NDBEVs 可能代表了针对神经退行性疾病进行特异性、可靠性和早期诊断的正确策略。基于这些结果，NDBEVs 可能能够为神经退行性疾病创建生前血液测试（大脑的液体活检）。这将极大地加速神经退行性疾病的治疗。本文综述强调了使用 NDBEVs 进行大脑液体活检在神经退行性疾病的早期诊断和治疗方面的强大潜力，并讨论了与使用血液识别临床适用的 EV（外泌体）生物标志物相关的挑战和局限性。
